Type 1 diabetes in North East England and North Cumbria: patterns and time trends in 0-14-year-olds from 2012 to 2020.

Introduction: It is important to understand patterns in the epidemiology of type 1 diabetes because they may provide insight into its etiology. We examined the incidence of type 1 diabetes in children aged 0-14 years, and patient demographics and clinical parameters at presentation, over the period 2012-2020 using the North East and North Cumbria Young Persons diabetes register. Methods: Patients up to the age of 14 years with type 1 diabetes, and their families- managed in a total of 18 young persons diabetes clinics-were approached in person at the time of clinic appointments or in the days following diagnosis and they consented to their data being included in the register. Data were submitted regionally to a central unit. Descriptive statistics including crude and age-specific incidence rates were calculated. Temporal trends were analyzed using Joinpoint regression. Comparisons in incidence rates were made between age, sex and areas of higher and lower affluence as measured by the Index of Multiple Deprivation (IMD). Results: A total of 943 cases were recorded between January 2012 and December 2020. Median age at diagnosis was 8.8 years (Q1: 5.3, Q3: 11.7). There were more males than females (54% male). The median HbA1c at diagnosis was 100 mmoL/L (IQR: 39) and over one third (35%) were in ketoacidosis (pH < 7.3). Crude incidence decreased from 25.5 (95% confidence interval [CI] 20.9, 29.9) in 2012 to 16.6 (95% CI: 13.0, 20.2) per 100,000 in 2020 (5.1% per annum, 95% CI 1.1, 8.8%). During the period of the study there was no evidence of any trends in median age, HbA1c, BMI or birthweight (p = 0.18, 0.80, 0.69, 0.32) at diagnosis. Higher rates were observed in males aged 10-14 years, but similar rates were found for both sexes aged 0-9 years and there was no difference between areas of higher or lower deprivation (p = 0.22). Conclusion: The incidence of diabetes in the young may be falling in the North East of England and North Cumbria. The reasons are unclear as there were no associations identified between levels of deprivation or anthropometric measurements. Potential mechanisms include alterations in socioeconomic background or growth pattern. Further research is needed to understand the reasons behind this finding.

Temporal clustering of neuroblastic tumours in children and young adults from Ontario, Canada.

BACKGROUND: The aetiology of neuroblastic tumours is likely to involve both genetic and environmental factors. A number of possible environmental risk factors have been suggested, including infection. If an irregular temporal pattern in incidence is found, this might suggest that a transient agent, such as an infection, is implicated. Previous work has found evidence for temporal clustering in children and young adults living in northern England. METHODS: We examined data from a second population-based registry from Ontario, Canada to determine whether there was evidence of temporal clustering of neuroblastic tumours. Cases diagnosed in children and young adults aged 0-19 years between 1985 and 2016 were extracted from the population-based Pediatric Oncology Group of Ontario Networked Information System (POGONIS). A modified version of the Potthoff-Whittinghill method was used to test for temporal clustering. Estimates of extra-Poisson variation (EPV) and standard errors (SE) were obtained. RESULTS: Eight hundred seventy-six cases of neuroblastic tumours were diagnosed during the study period. Overall, no evidence of temporal clustering was found between fortnights, between months or between quarters within years. However, significant EPV was found between years within the full study period (EPV = 1.05, SE = 0.25; P = 0.005). CONCLUSIONS: The findings are consistent with the possibility that a transient agent, such as an infection that is characterised by 'peaks and troughs' in its occurrence, might be implicated in the aetiology of neuroblastic tumours. However, this pattern may also reflect a long-term increase in the numbers of cases, rather than peaks and troughs.

Alcohol Screening and Brief Intervention in Police Custody Suites: Pilot Cluster Randomised Controlled Trial (AcCePT).

AIMS: There is a clear association between alcohol use and offending behaviour and significant police time is spent on alcohol-related incidents. This study aimed to test the feasibility of a trial of screening and brief intervention in police custody suites to reduce heavy drinking and re-offending behaviour. SHORT SUMMARY: We achieved target recruitment and high brief intervention delivery if this occurred immediately after screening. Low rates of return for counselling and retention at follow-up were challenges for a definitive trial. Conversely, high consent rates for access to police data suggested at least some outcomes could be measured remotely. METHODS: A three-armed pilot Cluster Randomised Controlled Trial with an embedded qualitative interview-based process evaluation to explore acceptability issues in six police custody suites (north east and south west of the UK). Interventions included: 1. Screening only (Controls), 2. 10 min Brief Advice 3. Brief Advice plus 20 min of brief Counselling. RESULTS: Of 3330 arrestees approached: 2228 were eligible for screening (67%) and 720 consented (32%); 386 (54%) scored 8+ on AUDIT; and 205 (53%) were enroled (79 controls, 65 brief advice and 61 brief counselling). Follow-up rates at 6 and 12 months were 29% and 26%, respectively. However, routinely collected re-offending data were obtained for 193 (94%) participants. Indices of deprivation data were calculated for 184 (90%) participants; 37.6% of these resided in the 20% most deprived areas of UK. Qualitative data showed that all arrestees reported awareness that participation was voluntary, that the trial was separate from police work, and the majority said trial procedures were acceptable. CONCLUSION: Despite hitting target recruitment and same-day brief intervention delivery, a future trial of alcohol screening and brief intervention in a police custody setting would only be feasible if routinely collected re-offending and health data were used for outcome measurement. TRIAL REGISTRATION: ISRCTN number: 89291046.

Behavior Change Techniques Used in Digital Behavior Change Interventions to Reduce Excessive Alcohol Consumption: A Meta-regression.

Background: Digital behavior change interventions (DBCIs) appear to reduce alcohol consumption, but greater understanding is needed of their mechanisms of action. Purpose: To describe the behavior change techniques (BCTs) used in DBCIs and examine whether individual BCTs, the inclusion of more BCTs or more Control Theory congruent BCTs is associated with increased effectiveness. Methods: Forty-one randomized control trials were extracted from a Cochrane review of alcohol reduction DBCIs and coded for up to 93 BCTs using an established and reliable method. Random effects unadjusted and adjusted meta-regression models were performed to assess associations between BCTs and intervention effectiveness. Results: Interventions used a mean of 9.1 BCTs (range 1-22), 23 different BCTs were used in four or more trials. Trials that used "Behavior substitution" (-95.112 grams per week [gpw], 95% CI: -162.90, -27.34), "Problem solving" (-45.92 gpw, 95% CI: -90.97, -0.87) and "Credible source" (-32.09 gpw, 95% CI: -60.64, -3.55) were significantly associated with greater alcohol reduction than trials without these BCTs. The "Behavior substitution" result should be treated as preliminary because it was reported in only four trials, three of which were conducted by the same research group. "Feedback" was used in 98% of trials (n = 41); other Control Theory congruent BCTs were used less frequently: for example, "Goal setting" 43% (n = 18) and "Self-monitoring" 29%, (n = 12). Conclusions: "Behavior substitution," "Problem solving," and "Credible source" were associated with greater alcohol reduction. Many BCTs were used infrequently in DBCIs, including BCTs with evidence of effectiveness in other domains, such as "Self-monitoring" and "Goal setting."

Rising global burden of breast cancer: the case of sub-Saharan Africa (with emphasis on Nigeria) and implications for regional development: a review.

BACKGROUND: Despite mortality from breast cancer in Africa being higher than in high income countries, breast cancer has not been extensively studied in the region. The aim of this paper was to highlight the rising burden of breast cancer with an emphasis on sub-Saharan Africa as well as trends, characteristics, controversies and their implications for regional development. METHODOLOGY: A review of published studies and documents was conducted in Medline, Scopus, Pubmed and Google using combinations of key words-breast neoplasm, breast cancer, cancer, incidence, mortality, Africa, Nigeria. Graphical and frequency analyses were carried out on some of the incidence and mortality figures retrieved from published papers and the GLOBOCAN website. FINDINGS: Globally, about 25% and 15% of all new cancer cases and cancer deaths respectively among females were due to breast cancer. Africa currently had the highest age-standardized breast cancer mortality rate globally, with the highest incidence rates being recorded within the sub-Saharan African sub-region. Incidence trends such as inherently aggressive tumour and younger age profile had been subject to controversies. Certain factors such as westernized diet, urbanization and possibly increasing awareness had been implicated, though their specific contributions were yet to be fully established. CONCLUSION: Unless urgent action is taken, breast cancer will compound sub-Saharan Africa's disease burden, increase poverty and gender inequality as well as reverse the current global gains against maternal and neonatal mortality.

Reported Theory Use by Digital Interventions for Hazardous and Harmful Alcohol Consumption, and Association With Effectiveness: Meta-Regression.

BACKGROUND: Applying theory to the design and evaluation of interventions is likely to increase effectiveness and improve the evidence base from which future interventions are developed, though few interventions report this. OBJECTIVE: The aim of this paper was to assess how digital interventions to reduce hazardous and harmful alcohol consumption report the use of theory in their development and evaluation, and whether reporting of theory use is associated with intervention effectiveness. METHODS: Randomized controlled trials were extracted from a Cochrane review on digital interventions for reducing hazardous and harmful alcohol consumption. Reporting of theory use within these digital interventions was investigated using the theory coding scheme (TCS). Reported theory use was analyzed by frequency counts and descriptive statistics. Associations were analyzed with meta-regression models. RESULTS: Of 41 trials involving 42 comparisons, half did not mention theory (50% [21/42]), and only 38% (16/42) used theory to select or develop the intervention techniques. Significant heterogeneity existed between studies in the effect of interventions on alcohol reduction (I2=77.6%, P<.001). No significant associations were detected between reporting of theory use and intervention effectiveness in unadjusted models, though the meta-regression was underpowered to detect modest associations. CONCLUSIONS: Digital interventions offer a unique opportunity to refine and develop new dynamic, temporally sensitive theories, yet none of the studies reported refining or developing theory. Clearer selection, application, and reporting of theory use is needed to accurately assess how useful theory is in this field and to advance the field of behavior change theories.

Effectiveness of brief alcohol interventions in primary care populations.

BACKGROUND: Excessive drinking is a significant cause of mortality, morbidity and social problems in many countries. Brief interventions aim to reduce alcohol consumption and related harm in hazardous and harmful drinkers who are not actively seeking help for alcohol problems. Interventions usually take the form of a conversation with a primary care provider and may include feedback on the person's alcohol use, information about potential harms and benefits of reducing intake, and advice on how to reduce consumption. Discussion informs the development of a personal plan to help reduce consumption. Brief interventions can also include behaviour change or motivationally-focused counselling.This is an update of a Cochrane Review published in 2007. OBJECTIVES: To assess the effectiveness of screening and brief alcohol intervention to reduce excessive alcohol consumption in hazardous or harmful drinkers in general practice or emergency care settings. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and 12 other bibliographic databases to September 2017. We searched Alcohol and Alcohol Problems Science Database (to December 2003, after which the database was discontinued), trials registries, and websites. We carried out handsearching and checked reference lists of included studies and relevant reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of brief interventions to reduce hazardous or harmful alcohol consumption in people attending general practice, emergency care or other primary care settings for reasons other than alcohol treatment. The comparison group was no or minimal intervention, where a measure of alcohol consumption was reported. 'Brief intervention' was defined as a conversation comprising five or fewer sessions of brief advice or brief lifestyle counselling and a total duration of less than 60 minutes. Any more was considered an extended intervention. Digital interventions were not included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We carried out subgroup analyses where possible to investigate the impact of factors such as gender, age, setting (general practice versus emergency care), treatment exposure and baseline consumption. MAIN RESULTS: We included 69 studies that randomised a total of 33,642 participants. Of these, 42 studies were added for this update (24,057 participants). Most interventions were delivered in general practice (38 studies, 55%) or emergency care (27 studies, 39%) settings. Most studies (61 studies, 88%) compared brief intervention to minimal or no intervention. Extended interventions were compared with brief (4 studies, 6%), minimal or no intervention (7 studies, 10%). Few studies targeted particular age groups: adolescents or young adults (6 studies, 9%) and older adults (4 studies, 6%). Mean baseline alcohol consumption was 244 g/week (30.5 standard UK units) among the studies that reported these data. Main sources of bias were attrition and lack of provider or participant blinding. The primary meta-analysis included 34 studies (15,197 participants) and provided moderate-quality evidence that participants who received brief intervention consumed less alcohol than minimal or no intervention participants after one year (mean difference (MD) -20 g/week, 95% confidence interval (CI) -28 to -12). There was substantial heterogeneity among studies (I² = 73%). A subgroup analysis by gender demonstrated that both men and women reduced alcohol consumption after receiving a brief intervention.We found moderate-quality evidence that brief alcohol interventions have little impact on frequency of binges per week (MD -0.08, 95% CI -0.14 to -0.02; 15 studies, 6946 participants); drinking days per week (MD -0.13, 95% CI -0.23 to -0.04; 11 studies, 5469 participants); or drinking intensity (-0.2 g/drinking day, 95% CI -3.1 to 2.7; 10 studies, 3128 participants).We found moderate-quality evidence of little difference in quantity of alcohol consumed when extended and no or minimal interventions were compared (-14 g/week, 95% CI -37 to 9; 6 studies, 1296 participants). There was little difference in binges per week (-0.08, 95% CI -0.28 to 0.12; 2 studies, 456 participants; moderate-quality evidence) or difference in days drinking per week (-0.45, 95% CI -0.81 to -0.09; 2 studies, 319 participants; moderate-quality evidence). Extended versus no or minimal intervention provided little impact on drinking intensity (9 g/drinking day, 95% CI -26 to 9; 1 study, 158 participants; low-quality evidence).Extended intervention had no greater impact than brief intervention on alcohol consumption, although findings were imprecise (MD 2 g/week, 95% CI -42 to 45; 3 studies, 552 participants; low-quality evidence). Numbers of binges were not reported for this comparison, but one trial suggested a possible drop in days drinking per week (-0.5, 95% CI -1.2 to 0.2; 147 participants; low-quality evidence). Results from this trial also suggested very little impact on drinking intensity (-1.7 g/drinking day, 95% CI -18.9 to 15.5; 147 participants; very low-quality evidence).Only five studies reported adverse effects (very low-quality evidence). No participants experienced any adverse effects in two studies; one study reported that the intervention increased binge drinking for women and two studies reported adverse events related to driving outcomes but concluded they were equivalent in both study arms.Sources of funding were reported by 67 studies (87%). With two exceptions, studies were funded by government institutes, research bodies or charitable foundations. One study was partly funded by a pharmaceutical company and a brewers association, another by a company developing diagnostic testing equipment. AUTHORS' CONCLUSIONS: We found moderate-quality evidence that brief interventions can reduce alcohol consumption in hazardous and harmful drinkers compared to minimal or no intervention. Longer counselling duration probably has little additional effect. Future studies should focus on identifying the components of interventions which are most closely associated with effectiveness.

A restatement of the natural science evidence base concerning the health effects of low-level ionizing radiation.

Exposure to ionizing radiation is ubiquitous, and it is well established that moderate and high doses cause ill-health and can be lethal. The health effects of low doses or low dose-rates of ionizing radiation are not so clear. This paper describes a project which sets out to summarize, as a restatement, the natural science evidence base concerning the human health effects of exposure to low-level ionizing radiation. A novel feature, compared to other reviews, is that a series of statements are listed and categorized according to the nature and strength of the evidence that underpins them. The purpose of this restatement is to provide a concise entrée into this vibrant field, pointing the interested reader deeper into the literature when more detail is needed. It is not our purpose to reach conclusions on whether the legal limits on radiation exposures are too high, too low or just right. Our aim is to provide an introduction so that non-specialist individuals in this area (be they policy-makers, disputers of policy, health professionals or students) have a straightforward place to start. The summary restatement of the evidence and an extensively annotated bibliography are provided as appendices in the electronic supplementary material.

Personalised digital interventions for reducing hazardous and harmful alcohol consumption in community-dwelling populations.

BACKGROUND: Excessive alcohol use contributes significantly to physical and psychological illness, injury and death, and a wide array of social harm in all age groups. A proven strategy for reducing excessive alcohol consumption levels is to offer a brief conversation-based intervention in primary care settings, but more recent technological innovations have enabled people to interact directly via computer, mobile device or smartphone with digital interventions designed to address problem alcohol consumption. OBJECTIVES: To assess the effectiveness and cost-effectiveness of digital interventions for reducing hazardous and harmful alcohol consumption, alcohol-related problems, or both, in people living in the community, specifically: (i) Are digital interventions more effective and cost-effective than no intervention (or minimal input) controls? (ii) Are digital interventions at least equally effective as face-to-face brief alcohol interventions? (iii) What are the effective component behaviour change techniques (BCTs) of such interventions and their mechanisms of action? (iv) What theories or models have been used in the development and/or evaluation of the intervention? Secondary objectives were (i) to assess whether outcomes differ between trials where the digital intervention targets participants attending health, social care, education or other community-based settings and those where it is offered remotely via the internet or mobile phone platforms; (ii) to specify interventions according to their mode of delivery (e.g. functionality features) and assess the impact of mode of delivery on outcomes. SEARCH METHODS: We searched CENTRAL, MEDLINE, PsycINFO, CINAHL, ERIC, HTA and Web of Knowledge databases; ClinicalTrials.com and WHO ICTRP trials registers and relevant websites to April 2017. We also checked the reference lists of included trials and relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated the effectiveness of digital interventions compared with no intervention or with face-to-face interventions for reducing hazardous or harmful alcohol consumption in people living in the community and reported a measure of alcohol consumption. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 57 studies which randomised a total of 34,390 participants. The main sources of bias were from attrition and participant blinding (36% and 21% of studies respectively, high risk of bias). Forty one studies (42 comparisons, 19,241 participants) provided data for the primary meta-analysis, which demonstrated that participants using a digital intervention drank approximately 23 g alcohol weekly (95% CI 15 to 30) (about 3 UK units) less than participants who received no or minimal interventions at end of follow up (moderate-quality evidence).Fifteen studies (16 comparisons, 10,862 participants) demonstrated that participants who engaged with digital interventions had less than one drinking day per month fewer than no intervention controls (moderate-quality evidence), 15 studies (3587 participants) showed about one binge drinking session less per month in the intervention group compared to no intervention controls (moderate-quality evidence), and in 15 studies (9791 participants) intervention participants drank one unit per occasion less than no intervention control participants (moderate-quality evidence).Only five small studies (390 participants) compared digital and face-to-face interventions. There was no difference in alcohol consumption at end of follow up (MD 0.52 g/week, 95% CI -24.59 to 25.63; low-quality evidence). Thus, digital alcohol interventions produced broadly similar outcomes in these studies. No studies reported whether any adverse effects resulted from the interventions.A median of nine BCTs were used in experimental arms (range = 1 to 22). 'B' is an estimate of effect (MD in quantity of drinking, expressed in g/week) per unit increase in the BCT, and is a way to report whether individual BCTs are linked to the effect of the intervention. The BCTs of goal setting (B -43.94, 95% CI -78.59 to -9.30), problem solving (B -48.03, 95% CI -77.79 to -18.27), information about antecedents (B -74.20, 95% CI -117.72 to -30.68), behaviour substitution (B -123.71, 95% CI -184.63 to -62.80) and credible source (B -39.89, 95% CI -72.66 to -7.11) were significantly associated with reduced alcohol consumption in unadjusted models. In a multivariable model that included BCTs with B > 23 in the unadjusted model, the BCTs of behaviour substitution (B -95.12, 95% CI -162.90 to -27.34), problem solving (B -45.92, 95% CI -90.97 to -0.87), and credible source (B -32.09, 95% CI -60.64 to -3.55) were associated with reduced alcohol consumption.The most frequently mentioned theories or models in the included studies were Motivational Interviewing Theory (7/20), Transtheoretical Model (6/20) and Social Norms Theory (6/20). Over half of the interventions (n = 21, 51%) made no mention of theory. Only two studies used theory to select participants or tailor the intervention. There was no evidence of an association between reporting theory use and intervention effectiveness. AUTHORS' CONCLUSIONS: There is moderate-quality evidence that digital interventions may lower alcohol consumption, with an average reduction of up to three (UK) standard drinks per week compared to control participants. Substantial heterogeneity and risk of performance and publication bias may mean the reduction was lower. Low-quality evidence from fewer studies suggested there may be little or no difference in impact on alcohol consumption between digital and face-to-face interventions.The BCTs of behaviour substitution, problem solving and credible source were associated with the effectiveness of digital interventions to reduce alcohol consumption and warrant further investigation in an experimental context.Reporting of theory use was very limited and often unclear when present. Over half of the interventions made no reference to any theories. Limited reporting of theory use was unrelated to heterogeneity in intervention effectiveness.

What helps or hinders midwives to implement physical activity guidelines for obese pregnant women? A questionnaire survey using the Theoretical Domains Framework.

OBJECTIVE: to investigate barriers and facilitators to physical activity (PA) guideline implementation for midwives when advising obese pregnant women. DESIGN: a cross-sectional, self-completion, anonymous questionnaire was designed using the Theoretical Domains Framework. this framework was developed to evaluate the implementation of guidelines by health care professionals. A total of 40 questions were included. These were informed by previous research on pregnant women's and midwives views, knowledge and attitudes to PA, and supported by national evidence based guidelines. Demographic information and free text comments were also collected. SETTING: three diverse NHS Trusts in the North East of England. PARTICIPANTS: all midwives employed by two hospital Trusts and the community midwives from the third Trust (n=375) were invited to participate. MEASUREMENTS: mean domain scores were calculated. Factor and regression analysis were performed to describe which theoretical domains may be influencing practice. Free text comments were analysed thematically. FINDINGS: 192 (53%) questionnaires were returned. Mean domain scores were highest for social professional role and knowledge, and lowest for skills, beliefs about capabilities and behaviour regulation. Regression analysis indicated that skills and memory/attention/decision domains had a statistically significant influence on midwives discussing PA with obese pregnant women and advising them accordingly. Midwives comments indicated that they felt it was part of their role to discuss PA with all pregnant women but felt they lacked the skills and resources to do so effectively. KEY CONCLUSIONS: midwives seem to have the necessary knowledge about the need/importance of PA advice for obese women and believe it is part of their role, but perceive they lack necessary skills and resources, and do not plan or prioritise the discussion regarding PA with obese pregnant woman. IMPLICATIONS FOR PRACTICE: designing interventions that improve skills, promote routine enquiry regarding PA and provide resources (eg. information, referral pathways) may help improve midwives' PA advice.

Does Industry-Driven Alcohol Marketing Influence Adolescent Drinking Behaviour? A Systematic Review.

AIM: To systematically review evidence on the influence of specific marketing components (Price, Promotion, Product attributes and Place of sale/availability) on key drinking outcomes (initiation, continuation, frequency and intensity) in young people aged 9-17. METHODS: MEDLINE, EMBASE, SCOPUS, PsychINFO, CINAHL and ProQuest were searched from inception to July 2015, supplemented with searches of Google Scholar, hand searches of key journals and backward and forward citation searches of reference lists of identified papers. RESULTS: Forty-eight papers covering 35 unique studies met inclusion criteria. Authors tended to report that greater exposure to alcohol marketing impacted on drinking initiation, continuation, frequency and intensity during adolescence. Nevertheless, 23 (66%) studies reported null results or negative associations, often in combination with positive associations, resulting in mixed findings within and across studies. Heterogeneity in study design, content and outcomes prevented estimation of effect sizes or exploration of variation between countries or age subgroups. The strength of the evidence base differed according to type of marketing exposure and drinking outcome studied, with support for an association between alcohol promotion (mainly advertising) and drinking outcomes in adolescence, whilst only two studies examined the relationship between alcohol price and the drinking behaviour of those under the age of 18. CONCLUSION: Despite the volume of work, evidence is inconclusive in all four areas of marketing but strongest for promotional activity. Future research with standardized measures is needed to build on this work and better inform interventions and policy responses.

Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review and economic assessment.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP - hyperemesis gravidarum (HG) - affects 0.3-1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG. OBJECTIVES: This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG. DATA SOURCES: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. Obstetric Medicine was hand-searched, as were websites of relevant organisations. Costs came from NHS sources. REVIEW METHODS: A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments. RESULTS: Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder (n = 20) it was unclear. The non-randomised studies (n = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo (n = 12); steroid versus usual treatment (n = 7); ginger versus placebo (n = 6); ginger versus vitamin B6 (n = 6); and vitamin B6 versus placebo (n = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin® [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices. LIMITATIONS: The main limitations were the quantity and quality of the data available. CONCLUSION: There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013006642. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Treatments for Hyperemesis Gravidarum and Nausea and Vomiting in Pregnancy: A Systematic Review.

Importance: Nausea and vomiting affects approximately 85% of pregnant women. The most severe form, hyperemesis gravidarum, affects up to 3% of women and can have significant adverse physical and psychological sequelae. Objective: To summarize current evidence on effective treatments for nausea and vomiting in pregnancy and hyperemesis gravidarum. Evidence Review: Databases were searched to June 8, 2016. Relevant websites and bibliographies were also searched. Titles and abstracts were assessed independently by 2 reviewers. Results were narratively synthesized; planned meta-analysis was not possible because of heterogeneity and incomplete reporting of findings. Findings: Seventy-eight studies (n = 8930 participants) were included: 67 randomized clinical trials (RCTs) and 11 nonrandomized studies. Evidence from 35 RCTs at low risk of bias indicated that ginger, vitamin B6, antihistamines, metoclopramide (for mild symptoms), pyridoxine-doxylamine, and ondansetron (for moderate symptoms) were associated with improved symptoms compared with placebo. One RCT (n = 86) reported greater improvements in moderate symptoms following psychotherapy (change in Rhodes score [range, 0 {no symptoms} to 40 {worst possible symptoms}], 18.76 [SD, 5.48] to 7.06 [SD, 5.79] for intervention vs 19.18 [SD, 5.63] to 12.81 [SD, 6.88] for comparator [P < .001]). For moderate-severe symptoms, 1 RCT (n = 60) suggested that pyridoxine-doxylamine combination taken preemptively reduced risk of recurrence of moderate-severe symptoms compared with treatment once symptoms begin (15.4% vs 39.1% [P < .04]). One RCT (n = 83) found that ondansetron was associated with lower nausea scores on day 4 than metoclopramide (mean visual analog scale [VAS] score, 4.1 [SD, 2.9] for ondansetron vs 5.7 [SD, 2.3] for metoclopramide [P = .023]) but not episodes of emesis (5.0 [SD, 3.1] vs 3.3 [SD, 3], respectively [P = .013]). Although there was no difference in trend in nausea scores over the 14-day study period, trend in vomiting scores was better in the ondansetron group (P = .042). One RCT (n = 159) found no difference between metoclopramide and promethazine after 24 hours (episodes of vomiting, 1 [IQR, 0-5] for metoclopramide vs 2 [IQR, 0-3] for promethazine [P = .81], VAS [0-10 scale] for nausea, 2 [IQR, 1-5] vs 2 [IQR, 1-4], respectively [P = .99]). Three RCTs compared corticosteroids with placebo or promethazine or metoclopramide in women with severe symptoms. Improvements were seen in all corticosteroid groups, but only a significant difference between corticosteroids vs metoclopramide was reported (emesis reduction, 40.9% vs 16.5% at day 2; 71.6% vs 51.2% at day 3; 95.8% vs 76.6% at day 7 [n = 40, P < .001]). For other interventions, evidence was limited. Conclusions and Relevance: For mild symptoms of nausea and emesis of pregnancy, ginger, pyridoxine, antihistamines, and metoclopramide were associated with greater benefit than placebo. For moderate symptoms, pyridoxine-doxylamine, promethazine, and metoclopramide were associated with greater benefit than placebo. Ondansetron was associated with improvement for a range of symptom severity. Corticosteroids may be associated with benefit in severe cases. Overall the quality of evidence was low.

Using Bayes factors for testing hypotheses about intervention effectiveness in addictions research.

BACKGROUND AND AIMS: It has been proposed that more use should be made of Bayes factors in hypothesis testing in addiction research. Bayes factors are the ratios of the likelihood of a specified hypothesis (e.g. an intervention effect within a given range) to another hypothesis (e.g. no effect). They are particularly important for differentiating lack of strong evidence for an effect and evidence for lack of an effect. This paper reviewed randomized trials reported in Addiction between January and June 2013 to assess how far Bayes factors might improve the interpretation of the data. METHODS: Seventy-five effect sizes and their standard errors were extracted from 12 trials. Seventy-three per cent (n = 55) of these were non-significant (i.e. P > 0.05). For each non-significant finding a Bayes factor was calculated using a population effect derived from previous research. In sensitivity analyses, a further two Bayes factors were calculated assuming clinically meaningful and plausible ranges around this population effect. RESULTS: Twenty per cent (n = 11) of the non-significant Bayes factors were < â…“ and 3.6% (n = 2) were > 3. The other 76.4% (n = 42) of Bayes factors were between ⅓ and 3. Of these, 26 were in the direction of there being an effect (Bayes factor > 1 and < 3); 12 tended to favour the hypothesis of no effect (Bayes factor < 1 and > â…“); and for four there was no evidence either way (Bayes factor = 1). In sensitivity analyses, 13.3% of Bayes Factors were < â…“ (n = 20), 62.7% (n = 94) were between ⅓ and 3 and 24.0% (n = 36) were > 3, showing good concordance with the main results. CONCLUSIONS: Use of Bayes factors when analysing data from randomized trials of interventions in addiction research can provide important information that would lead to more precise conclusions than are obtained typically using currently prevailing methods.

Critical care admission trends and outcomes in individuals with bronchiectasis in the UK.

BACKGROUND: There are limited data on admission trends and outcomes of individuals with bronchiectasis admitted to intensive care (ICU). Using national critical care data, we analysed admissions to ICU and estimated outcomes in terms of mortality in individuals with bronchiectasis and chronic obstructive pulmonary disease (COPD) admitted to ICU. METHODS: Using data from the Intensive Care National Audit and Research Centre, admissions from bronchiectasis and COPD from 1 January 2009 to 31 December 2013 were extracted. Crude admission rates for bronchiectasis and COPD were calculated and Poisson regression was used to estimate unadjusted annual admission rate ratios. We investigated changes to length of stay on ICU, ICU mortality and in-hospital mortality during the study period. We also compared mortality rates in people with bronchiectasis and COPD aged 70 or above. RESULTS: We found an annual increase of 8% (95% Confidence Interval [CI] 2-15) in the number of ICU admissions from bronchiectasis, whilst the yearly increase in ICU admissions from COPD was 1% (95% CI 0.3-2). ICU and in-hospital mortality was higher in individuals with bronchiectasis compared with those with COPD, especially in people aged 70 years or above. CONCLUSION: Admission to ICU in people with bronchiectasis are uncommon, but are increasing in frequency over time, and carries a substantial mortality rate. This needs to be considered allocating health care resources and planning respiratory services.

Does primary biliary cirrhosis cluster in time?

The aetiology of primary biliary cirrhosis (PBC) is not well established. Previously we found evidence of space-time clustering and seasonal variation in the date of diagnosis, suggesting a possible role for a transient or seasonally varying environmental factor. We examined whether a temporally varying environmental agent may be involved by analysing population-based PBC data from northeast England over 1987-2003. Using an adaptation of a method proposed by Potthoff and Whittinghill, we found significant temporal variation by date of diagnosis at the level of aggregation of one year. However, there was no evidence for general irregular (non-seasonal) temporal clustering within periods less than a year. These results provide little support for the involvement of agents occurring in geographically widespread mini-epidemics, but--taken together with studies of spatial and spatio-temporal clustering--do not preclude the role of more localised sporadic mini-epidemics. Future research should seek to elicit putative environmental agents.

Temporal clustering of neuroblastic tumours in children and young adults from Northern England.

BACKGROUND: The aetiology of neuroblastic tumours is unclear with both genetic and environmental factors implicated. The possibility that an infectious agent may be involved has been suggested. 'Temporal clustering' occurs if cases display an irregular temporal distribution and may indicate the involvement of an agent that exhibits epidemicity. We tested for the presence and nature of temporal clustering using population-based data from northern England. METHODS: We extracted all cases of neuroblastic tumours diagnosed in children and young adults aged 0-24 years during 1968-2011 from the Northern Region Young Persons' Malignant Disease Registry. This is a population-based registry, covering a population of approximately 900,000 young persons, and includes all cases resident in northern England at the time of diagnosis. Tests for temporal clustering were applied using a modified version of the Potthoff-Whittinghill method. Estimates of extra-Poisson variation (ß) and standard errors (SEs) were obtained. RESULTS: 227 cases of neuroblastic tumours were diagnosed during the study period. All the analyses between fortnights and between months found significant extra-Poisson variation, with ß = 0.846 (SE = 0.310, P = 0.004) for the analysis between fortnights within months. Restricting the analyses to the 76 cases diagnosed at ages less than 18 months showed significant extra-Poisson variation between fortnights within months (ß = 1.532, SE = 0.866, P = 0.038), but not between months. In contrast, analyses of cases aged 18 months to 24 years showed significant extra-Poisson variation between quarters within years, as well as over shorter timescales. CONCLUSIONS: Transient environmental agents may be involved in the aetiology of neuroblastic tumours. The initiating factor might be a geographically-widespread agent that occurs in 'mini-epidemics'.

Calculation of lifetime lung cancer risks associated with radon exposure, based on various models and exposure scenarios.

The risk of lung cancer mortality up to 75 years of age due to radon exposure has been estimated for both male and female continuing, ex- and never-smokers, based on various radon risk models and exposure scenarios. We used risk models derived from (i) the BEIR VI analysis of cohorts of radon-exposed miners, (ii) cohort and nested case-control analyses of a European cohort of uranium miners and (iii) the joint analysis of European residential radon case-control studies. Estimates of the lifetime lung cancer risk due to radon varied between these models by just over a factor of 2 and risk estimates based on models from analyses of European uranium miners exposed at comparatively low rates and of people exposed to radon in homes were broadly compatible. For a given smoking category, there was not much difference in lifetime lung cancer risk between males and females. The estimated lifetime risk of radon-induced lung cancer for exposure to a concentration of 200 Bq m(-3) was in the range 2.98-6.55% for male continuing smokers and 0.19-0.42% for male never-smokers, depending on the model used and assuming a multiplicative relationship for the joint effect of radon and smoking. Stopping smoking at age 50 years decreases the lifetime risk due to radon by around a half relative to continuing smoking, but the risk for ex-smokers remains about a factor of 5-7 higher than that for never-smokers. Under a sub-multiplicative model for the joint effect of radon and smoking, the lifetime risk of radon-induced lung cancer was still estimated to be substantially higher for continuing smokers than for never smokers. Radon mitigation-used to reduce radon concentrations at homes-can also have a substantial impact on lung cancer risk, even for persons in their 50 s; for each of continuing smokers, ex-smokers and never-smokers, radon mitigation at age 50 would lower the lifetime risk of radon-induced lung cancer by about one-third. To maximise risk reductions, smokers in high-radon homes should both stop smoking and remediate their homes.